Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31

被引：132

作者：

Gelmon, Karen A. ^{[1
]}

Boyle, Frances M. ^{[9
]}

Kaufman, Bella ^{[10
]}

Huntsman, David G. ^{[1
]}

Manikhas, Alexey ^{[12
]}

Di Leo, Angelo ^{[15
]}

Martin, Miguel ^{[16
]}

Schwartzberg, Lee S. ^{[17
]}

Lemieux, Julie ^{[3
]}

Aparicio, Samuel ^{[1
]}

Shepherd, Lois E. ^{[4
]}

Dent, Susan ^{[5
]}

Ellard, Susan L. ^{[2
]}

Tonkin, Katia ^{[8
]}

Pritchard, Kathleen I. ^{[6
]}

Whelan, Timothy J. ^{[7
]}

Nomikos, Dora ^{[4
]}

Nusch, Arnd

Coleman, Robert E. ^{[18
]}

Mukai, Hirofumi ^{[19
]}

Tjulandin, Sergei ^{[13
]}

Khasanov, Rustem ^{[14
]}

Rizel, Shulamith ^{[11
]}

Connor, Anne P. ^{[20
]}

Santillana, Sergio L. ^{[21
]}

Chapman, Judith-Anne W. ^{[4
]}

Parulekar, Wendy R. ^{[4
]}

机构：

[1] British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada

[2] British Columbia Canc Agcy, Canc Ctr Southern Interior, Kelowna, BC, Canada

[3] Ctr Hosp Affilie Hop Du St Sacrement, Quebec City, PQ, Canada

[4] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada

[5] Ottawa Hlth Res Inst, Ottawa, ON, Canada

[6] Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON M4N 3M5, Canada

[7] Hamilton Hlth Sci, Juravinski Canc Ctr, Hamilton, ON, Canada

[8] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada

[9] Mater Hosp, Patricia Ritchie Ctr Canc Care & Res, Sydney, NSW, Australia

[10] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel

[11] Rabin Med Ctr, Petah Tiqwa, Israel

[12] City Clin Oncol Dispensery, St Petersburg, Russia

[13] Russian Canc Res Ctr, Moscow, Russia

[14] Clin Oncol Dispensary, Kazan, Russia

[15] Sandro Pitgliani Med Oncol Unit, Prato, Italy

[16] Serv Oncol Hosp Gregorio Maranon, Madrid, Spain

[17] West Clin, Memphis, TN USA

[18] Weston Pk Hosp, Canc Res Ctr, Sheffield, S Yorkshire, England

[19] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan

[20] GlaxoSmithKline, Collegeville, PA USA

[21] GlaxoSmithKline, Rio De Janeiro, Brazil

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 14期

关键词：

ADJUVANT CHEMOTHERAPY; 1ST-LINE TREATMENT; PHASE-III; PACLITAXEL; DOCETAXEL; CAPECITABINE; COMBINATION; PLACEBO; WOMEN; TRIAL;

D O I：

10.1200/JCO.2014.56.9590

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown. Patients and Methods The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors. Results From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03). Conclusion As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane. (C) 2015 by American Society of Clinical Oncology

引用

页码：1574 / +

页数：14

共 32 条

[1] Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration [J].

Altman, Douglas G. ;

McShane, Lisa M. ;

Sauerbrei, Willi ;

Taube, Sheila E. .

PLOS MEDICINE, 2012, 9 (05)

[2] Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study [J].

Bachelot, Thomas ;

Romieu, Gilles ;

Campone, Mario ;

Dieras, Veronique ;

Cropet, Claire ;

Dalenc, Florence ;

Jimenez, Marta ;

Le Rhun, Emilie ;

Pierga, Jean-Yves ;

Goncalves, Anthony ;

Leheurteur, Marianne ;

Domont, Julien ;

Gutierrez, Maya ;

Cure, Herve ;

Ferrero, Jean-Marc ;

Labbe-Devilliers, Catherine .

LANCET ONCOLOGY, 2013, 14 (01) :64-71

[3] Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial [J].

Baselga, Jose ;

Bradbury, Ian ;

Eidtmann, Holger ;

Di Cosimo, Serena ;

de Azambuja, Evandro ;

Aura, Claudia ;

Gomez, Henry ;

Dinh, Phuong ;

Fauria, Karine ;

Van Dooren, Veerle ;

Aktan, Gursel ;

Goldhirsch, Aron ;

Chang, Tsai-Wang ;

Horvath, Zsolt ;

Coccia-Portugal, Maria ;

Domont, Julien ;

Tseng, Ling-Min ;

Kunz, Georg ;

Sohn, Joo Hyuk ;

Semiglazov, Vladimir ;

Lerzo, Guillermo ;

Palacova, Marketa ;

Probachai, Volodymyr ;

Pusztai, Lajos ;

Untch, Michael ;

Gelber, Richard D. ;

Piccart-Gebhart, Martine .

LANCET, 2012, 379 (9816) :633-640

[4] Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer [J].

Baselga, Jose ;

Cortes, Javier ;

Kim, Sung-Bae ;

Im, Seock-Ah ;

Hegg, Roberto ;

Im, Young-Hyuck ;

Roman, Laslo ;

Pedrini, Jose Luiz ;

Pienkowski, Tadeusz ;

Knott, Adam ;

Clark, Emma ;

Benyunes, Mark C. ;

Ross, Graham ;

Swain, Sandra M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (02) :109-119

[5] Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study [J].

Blackwell, Kimberly L. ;

Burstein, Harold J. ;

Storniolo, Anna Maria ;

Rugo, Hope S. ;

Sledge, George ;

Aktan, Gursel ;

Ellis, Catherine ;

Florance, Allison ;

Vukelja, Svetislava ;

Bischoff, Joachim ;

Baselga, Jose ;

O'Shaughnessy, Joyce .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (21) :2585-2592

[6] The distinctive nature of HER2-positive breast cancers [J].

Burstein, HJ .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (16) :1652-1654

[7] A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses [J].

Cameron, David ;

Casey, Michelle ;

Press, Michael ;

Lindquist, Deborah ;

Pienkowski, Tadeusz ;

Romieu, C. Gilles ;

Chan, Stephen ;

Jagiello-Gruszfeld, Agnieszka ;

Kaufman, Bella ;

Crown, John ;

Chan, Arlene ;

Campone, Mario ;

Viens, Patrice ;

Davidson, Neville ;

Gorbounova, Vera ;

Raats, Johannes Isaac ;

Skarlos, Dimosthenis ;

Newstat, Beth ;

Roychowdhury, Debasish ;

Paoletti, Paolo ;

Oliva, Cristina ;

Rubin, Stephen ;

Stein, Steven ;

Geyer, Charles E. .

BREAST CANCER RESEARCH AND TREATMENT, 2008, 112 (03) :533-543

[8] Survival differences among women with de novo stage IV and relapsed breast cancer [J].

Dawood, S. ;

Broglio, K. ;

Ensor, J. ;

Hortobagyi, G. N. ;

Giordano, S. H. .

ANNALS OF ONCOLOGY, 2010, 21 (11) :2169-2174

[9] Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer [J].

Di Leo, Angelo ;

Gomez, Henry L. ;

Aziz, Zeba ;

Zvirbule, Zanete ;

Bines, Jose ;

Arbushites, Michael C. ;

Guerrera, Stephanie F. ;

Koehler, Maria ;

Oliva, Cristina ;

Stein, Steven H. ;

Williams, Lisa S. ;

Dering, Judy ;

Finn, Richard S. ;

Press, Michael F. .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (34) :5544-5552

[10] Bias correction for score tests arising from misspecified proportional hazards regression models [J].

DiRienzo, AG ;

Lagakos, SW .

BIOMETRIKA, 2001, 88 (02) :421-434

← 1 2 3 4 →